Periodontal disease is an oral inflammatory disease that begins when inflammation of gingival tissues (gingivitis) progresses to an inflammation of the periodontal attachment tissues. This inflammation may eventually lead to breakdown of the periodontal attachment, periodontal pocket formation and bone loss-periodontitis. The disease may progress to the extent of causing tooth loss due to destruction of the tooth supporting bone. A similar course of events can take place in the tissues surrounding dental implants (peri-implantitis), and can result in gradual loosening and eventual loss of the implant.
The rate of progression of periodontal disease is extremely variable. It is believed to be modulated by a complex interaction between subgingival bacterial, the host defense system (including immune and inflammatory responses), and other local tissue factors. Methods of treatment, however, have traditionally focused on the bacterial component of the disease.
The conventional approach to the treatment of periodontal disease involves initially removing subgingival bacterial plaque and calculus deposits with scaling and root planing procedures and following-up with improved oral hygiene procedures. If this treatment does not halt progression of the disease, surgical reduction of periodontal tissues is often performed, with the intention of decreasing the depth of the periodontal pocket, thus decreasing the area available for bacterial colonization and aiding mechanical removal of the microorganisms. Concurrent treatment with an antibacterial agent may also be used to further reduce bacterial numbers.
Antibiotics such as tetracycline derivatives are commonly used. These drugs are either administered systemically, or, more recently, they are introduced directly into the periodontal pocket by site-specific drug delivery methods utilizing a polymeric matrix material as a carrier. Such products include Atridox.RTM. and Actisite.RTM.. Another agent, chlorohexidine gluconate (an antiseptic) has been formulated into a gelatin/glutaraldehyde matrix in the form of a small chip, the Periochip.RTM., which delivers a bactericidal dose of chlorohexidine to the periodontal pocket. With these methods, drug concentrations in the periodontal pocket are much higher than could be attained by systemic dosing. These systems provide a sustained release of the drug in the periodontal pocket over a 7 to 10 day course of treatment. They are more difficult to administer than an oral antibacterial agent, but by delivering a high, sustained dose over the course of treatment, the site-specific systems are less likely to cause bacterial resistance development, which is problematic with long-term systemic antimicrobial treatment.
While these systems offer a possible alternative to periodontal surgery for treatment of refractory sites that have not responded to scaling and root planing procedures, the overall strategy of treatment of periodontal disease with antibacterial agents alone may be questioned. Although periodontal disease may be initiated by the presence of certain microorganisms, the present invention recognizes that it is an inflammatory condition that may be more effectively treated by attempting to decrease or eliminate the inflammatory response to the bacteria rather than the bacteria itself.
A variety of non-steroidal anti-inflammatory drugs (NSAIDs) have been studied as treatments for periodontal disease. These studies have examined NSAIDs delivered either topically, site-specifically or systemically and some have been found to exhibit limited beneficial effects. However, the NSAIDs only block the cyclooxygenase pathway in the metabolism of arachidonic acid, thereby blocking formation of only a portion of the inflammatory mediators. When used systemically, NSAIDs also may cause gastrointestinal side effects, which would be prohibitive for long-term treatment. No NSAID is currently marketed specifically for the treatment of periodontal disease.
Recently, Periostat.RTM. has been introduced for the treatment of periodontal disease. Periostat.RTM. is a low-dose formulation of doxycycline. Although doxycycline is known for its antimicrobial properties, at the low dosages present in Periostat.RTM., its effects are due to inhibition of collagenase enzymes. Periostat.RTM. shows no antibacterial activity at the prescribed dosage. The clinical studies show results similar to those obtained with local delivery of antibacterial agents.
The current methods for treatment of periodontal disease are costly, painful and often ineffective, discouraging many from seeking treatment. Of all the above-mentioned products, none provide a significant impact on the treatment of periodontal disease. A need therefore exists for such a product. The compositions and methods described herein addresses this need.